Dr. Jenkins is an Infectious Diseases specialist three years out of fellowship and director of the Antibiotic Stewardship Program at Denver Health. His clinical and research interests have focused on improving antibiotic use for the treatment of bloodstream and skin and soft tissue infections (SSTIs). His long-term career goal is to become a leader in the design and implementation of federally-funded clinical trials that define optimal treatment strategies for invasive bacterial infections, thus promoting more judicious antibiotic use. The dual threat of progressive antimicrobial resistance and the declining rate of new antibiotic development has highlighted the need for strategies to conserve current antibacterial agents. SSTIs are among the most common infections leading to hospitalization and result in a substantial amount of unnecessary antibiotic use. The objective of the proposed research is to provide data essential to direct antibiotic stewardship efforts, design federally-funded clinical trials of interventions to decrease antibiotic exposure for SSTIs, and strengthen clinical trial design for new antibiotic development. A generalizable knowledge of antibiotic prescribing practices is of fundamental importance to develop antibiotic stewardship initiatives and frame clinical trials to improve treatment of SSTIs. In order to gain a better understanding of antibioti use for SSTIs in the hospital setting, a multi-institutional retrospective cohort study will be performed to describe antibiotic prescribing practices across diverse institutions and evaluate factors associated with use of excessively broad-spectrum and prolonged treatment courses. There is controversy regarding the design of clinical trials for SSTIs because of a lack of contemporary data regarding their natural history. A prospective observational cohort study will be performed to characterize the time course of resolution of signs and symptoms of infection, identify clinical factors associated with adverse outcomes, and evaluate endpoint definitions in patients hospitalized with cellulitis/erysipelas, major cutaneous abscess, and wound infection The assessment of clinical response and decision of treatment duration for patients hospitalized with SSTI is frequently challenging on clinical grounds alone. Biomarker-guided treatment strategies have promise to improve antibiotic prescribing but have not been studied in SSTIs. The proposed studies will characterize serum biomarkers, including C-reactive protein, procalcitonin, and selected cytokines during the treatment of patients hospitalized with SSTI and assess their utility as markers of treatment response. In summary, the proposed research will provide essential data to move the field of SSTI research forward while facilitating Dr. Jenkins' development into an independently funded investigator. Project Narrative Antibiotic resistance in bacteria is becoming more widespread while the development of new antibiotics has dramatically slowed. It is imperative that antibiotics are used judiciously to conserve the effectiveness of current drugs for as long as possible. Skin infections such as cellulitis, abscesses, and wound infections are among the most common infections treated in hospitals and result in a substantial amount of unnecessary antibiotic use. The proposed research will generate a broader understanding of antibiotic prescribing practices across hospitals, the response to treatment and predictors of poor outcomes, and the role of serum proteins as markers of treatment response for skin infections. The information obtained will inform the design of antibiotic conservation efforts and future clinical trials to identify treatment strategis that promote more judicious use of antibiotics.